US2004047880A1PendingUtilityA1

Component for vaccine

42
Priority: Oct 3, 2000Filed: Oct 3, 2001Published: Mar 11, 2004
Est. expiryOct 3, 2020(expired)· nominal 20-yr term from priority
Inventors:Xavier De BolleJean-Jacques LetessonYves LobetPascal MertensJan PoolmanPierre Voet
C07K 14/22A61K 39/095G01N 2333/22G01N 33/6878G01N 33/6854A61P 31/04G01N 2400/50C07K 16/1217
42
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Claims

Abstract

The present invention relates to a component for a vaccine against menigococci, in particular peptides which mimic epitopes of meningococcal lipooligosaccharide, and to a vaccine comprising such a component.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A mimotope of a surface L3,7,9 LOS of  N. meningitidis , said mimotope comprising a peptide epitope obtainable by screening a peptide library with a monoclonal antibody selected from a group consisting of: 4BE12C10; H44/24; H44/58; H44/70; and H44/78.  
     
     
         2 . A mimotope of a surface L3,7,9 LOS of  N. meningitidis , said mimotope being antigenically cross-reactive with a monoclonal antibody selected from a group consisting of: 4BE12C10; H44/24; H44/58; H44/70; and H44/78.  
     
     
         3 . The mimotope according to  claim 1  or  claim 2 , which comprises a peptide epitope contained within any one of the peptides of SEQ ID NO: 1-140, 289-296, or retro sequences thereof.  
     
     
         4 . The mimotope according to  claim 3 , wherein the peptide epitope is present in a nonapeptide.  
     
     
         5 . The mimotope according to claims  3 - 4 , which comprises any one of the peptides of SEQ ID NO: 1-140, 289-296, or retro sequences thereof, or modifications of the peptides or retro sequences which retain cross-reactivity with a monoclonal antibody selected from a group consisting of: 4BE12C10; H44/24; H44/58; H44/70; and H44/78.  
     
     
         6 . The mimotope of claims  3 - 5 , wherein the peptide epitope comprises the amino acid sequence PP[Y or F or W].  
     
     
         7 . The mimotope of  claim 6 , wherein the peptide epitope comprises the amino acid sequence PP[Y or F or W]D.  
     
     
         8 . The mimotope of  claim 7 , wherein the peptide epitope comprises the amino acid sequence PPYD.  
     
     
         9 . The mimotope of claims  3 - 5 , wherein the peptide epitope comprises the amino acid sequence WY.  
     
     
         10 . The mimotope of  claim 9 , wherein the peptide epitope comprises the amino acid sequence WYXXP.  
     
     
         11 . The mimotope of claims  3 - 5 , wherein the peptide epitope comprises the amino acid sequence [Y or W]XY.  
     
     
         12 . The mimotope of claims  3 - 11 , wherein said mimotope comprises an oligopeptide, comprising said peptide epitope, which is structurally more constrained than an unsubstituted linear form of the oligopeptide.  
     
     
         13 . The mimotope according to  claim 12 , wherein the oligopeptide comprises a cyclic peptide encompassing the peptide epitope.  
     
     
         14 . The mimotope according to  claim 13 , wherein the cyclic peptide comprises a cyclised portion which comprises an amino acid sequence, the terminal amino acids of which are linked together by a covalent bond.  
     
     
         15 . The mimotope according to  claim 14 , wherein the cyclic peptide is any one of the peptides of SEQ ID NO: 141-280, 297-301, or retro sequences thereof.  
     
     
         16 . The mimotope according to any one of the preceding claims, wherein a carrier is conjugated to the mimotope to enhance the immunogenicity thereof.  
     
     
         17 . The mimotope according to  claim 16 , wherein the carrier comprises an immunogenic protein.  
     
     
         18 . A vaccine comprising a mimotope according to any one of the preceding claims and a suitable excipient or diluent.  
     
     
         19 . A vaccine against serogroup B, C, Y, or W-135 meningococci, which comprises a mimotope of a surface L3,7,9 LOS of  N. meningitidis  and a mimotope of a surface L2 LOS of  N. meningitidis.    
     
     
         20 . The vaccine according to  claim 19 , wherein the mimotopes are antigenically cross-reactive with a monoclonal antibody of high specificity to the respective surface LOS.  
     
     
         21 . The vaccine according to  claim 19  or  claim 20 , wherein the mimotopes each comprise a peptide epitope.  
     
     
         22 . The vaccine according to  claim 21 , wherein the peptide epitopes are obtainable by screening a peptide library with the respective monoclonal antibodies of  claim 20 .  
     
     
         23 . The vaccine of  claim 21  or  22 , wherein the L3,7,9 and the L2 mimotopes are contained within the same molecule.  
     
     
         24 . The vaccine according to claims  21 - 23 , wherein the mimotope of a surface L3,7,9 LOS is the mimotope of claims  2 - 17 .  
     
     
         25 . The vaccine according to claims  21 - 23 , wherein the mimotope of a surface L3,7,9 LOS comprises a peptide selected from: 
 IHRQGIH; HIGQRHI; LPARTEG; GETRAPL; APARQLP; PLQRAPA; KQAPVHH; HHVPAQK; LQAPVHH; HHVPAQL; LPSIQLP; PLQISPL; NELPHKL; LKHPLEN; KSPSMTL; LTMSPSK; AGPLMLL; LLMLPGA; WSPILLD DLLIPSW; LSMHPQN; NQPHMSL; HSMHPQN NQPHMSH; SMYGSYN; NYSGYMS; TNHSLYH; HYLSHNT; HAIYPRH; HRPYIAH; TTYSRFP; PFRSYTT; TDSLRLL; LLRLSDT; SFATNIP; and PINTAFS.    
     
     
         26 . The vaccine according to claim  19 - 25 , wherein the mimotope of a surface L2 LOS is antigenically cross-reactive with F1-5H 5/ID9 monoclonal antibody.  
     
     
         27 . A vaccine against serogroup A meningococci, which comprises a mimotope of a surface L3,7,9 LOS of  N. meningitidis  and a mimotope of a surface L10 LOS of  N. meningitidis.    
     
     
         28 . The vaccine according to  claim 27 , wherein the mimotope of a surface L10 LOS is antigenically cross-reactive with a monoclonal antibody of high specificity to the L10 LOS.  
     
     
         29 . The vaccine according to  claim 28 , wherein the monoclonal antibody is 5B4-F9-B10.  
     
     
         30 . The vaccine of  claim 28  or  29 , wherein the mimotope of a surface L10 LOS comprises a peptide epitope.  
     
     
         31 . A meningococcal vaccine comprising a mimotope of a surface L3,7,9 LOS of  N. meningitidis,  a mimotope of a surface L10 LOS of  N. meningitidis,  and a mimotope of a surface L2 LOS of  N. meningitidis.    
     
     
         32 . A meningitis vaccine comprising the vaccine of  claim 31 , and a conjugated  H. influenzae  b capsular polysaccharide.  
     
     
         33 . A H44/24 hybridoma deposited under the Budapest Treaty patent deposit at ECACC on 22/9/00 with Provisional Accession Number 92209.  
     
     
         34 . A H44/58 hybridoma deposited under the Budapest Treaty patent deposit at ECACC on 22/9/00 with Provisional Accession Number 92210.  
     
     
         35 . A H44/70 hybridoma deposited under the Budapest Treaty patent deposit at ECACC on 22/9/00 with Provisional Accession Number 92211.  
     
     
         36 . A H44/78 hybridoma deposited under the Budapest Treaty patent deposit at ECACC on 22/9/00 with Provisional Accession Number 92212.  
     
     
         37 . A monoclonal antibody obtainable from any of the hybridomas of claims  33 - 36 .  
     
     
         38 . Use of the monoclonal antibodies of  claim 37  in the identification of mimotopes of  N. meningitidis  L3,7,9 LOS.  
     
     
         39 . A pharmaceutical composition comprising the monoclonal antibody of  claim 37 .  
     
     
         40 . A mimotope as described in claims  1 - 17 , or a vaccine as described in claims  18 - 32 , or a monoclonal antibody as described in  claim 37  for use as a medicament.  
     
     
         41 . Use of the mimotope of claims  1 - 17 , or the vaccine of claims  18 - 32 , or the monoclonal antibody of  claim 37  in the manufacture of a medicament for the treatment or prevention of meningococcal disease.  
     
     
         42 . A method of manufacturing a vaccine comprising the manufacture of a mimotope as claimed in any one of  claims 1  to  17 , and formulating the mimotope with an adjuvant.  
     
     
         43 . A method for treating a patient suffering from or susceptible to meningococcal disease, comprising the administration of the mimotope of claims  1 - 17 , or the vaccine of claims  18 - 32 , or the monoclonal antibody of  claim 37 , to the patient.  
     
     
         44 . A DNA sequence encoding the mimotope of claims  1 - 16 .  
     
     
         45 . A diagnostic assay for meningococcal infection comprising the use of the mimotope of claims  1 - 16  to detect antibodies against L3,7,9 LOS in the serum of a patient.  
     
     
         46 . A diagnostic assay for meningococcal infection comprising the use of the monoclonal antibody of  claim 37  to detect the presence of L3,7,9 immunotype meningococcus in a sample from a patient.  
     
     
         47 . A DNA sequence encoding a CDR region encoded by the DNA sequences of SEQ ID NO:281-288.

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